Melanomas are aggressive, frequently metastatic tumors derived from either melanocytes or melanocyte related nevus cells. Melanomas represent approximately three percent of all skin cancers and even when it is apparently localized to the skin, up to 30% of the patients will develop systemic metastasis. Classic modalities of treating melanoma include surgery, radiation and chemotherapy. Then immunotherapy and gene therapy have emerged as promising methods for treating melanoma. Rosenberg's results showed that adoptive transfer into patients with metastatic melanoma of tumor infiltrating lymphocytes (TIL) that recognize cancer antigens, are able to mediate the regression of metastatic cancer in 35 to 40% of melanoma patients.
In the last twenty years, many human melanoma antigens recognized by T cells have been identified using various methods such as cDNA cloning, MHC-bound peptide purification or T cell induction against candidate peptides or proteins. These antigens have been classified in several groups: melanocytic differentiation antigens (such as Melan-A/MART-1) (1), cancer-germline antigens, shared by several tumors and male germline cells (such as MAGE antigens) (2, 3), mutated antigens generated by genetic alterations (such as CDK4) (4), antigens overexpressed in various tumor types (such as PRAME) (5), and antigens aberrantly expressed in tumors (such as NA17-A and NA88-A) (6, 7). However, despite their high number, the immunogenicity of these antigens has not been elucidated yet, with the exception of Melan-A/MART-1. Indeed, the immunogenicity of the Melan-A antigen in melanoma has been strongly suggested by the analysis of several active (8, 9) and passive (10-15) immunotherapy protocols targeting this antigen.
The identification of additional melanoma antigens with a documented immunogenic potential remains a major issue to address for cancer immunotherapy, especially for melanoma.